Insulin-like Growth Factor Binding Protein Expression in Human Retinal Pigment Epithelial Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73426/1/j.1749-6632.1993.tb26229.x.pd

Receptor-Coupled Phosphoinositide Hydrolysis in Human Retinal Pigment Epithelium

Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of 3 H-inositol phosphates in the presence of 10 m M Li + . Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC 50 of 60 Μ M ; stimulation was linear up to 60 min. This activation likely occurred via the M 3 muscarinic cholinergic receptor based on the IC 50 values for 4-diphenylacetoxy- N -methylpiperidine methiodide (0.47 n M ), pirenzepine (280 n M ), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6 H -pyrido[2,3- b ][1,4]benzodiazepin-6-one (1.4 Μ M ). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca 2+ . Histamine stimulated PPI turnover in a linear manner by 180% with an EC 50 of 20 Μ M by the H 1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca 2+ concentration, as determined by fura-2 fluorescence, was 138 ± 24 n M . On the addition of carbachol, there was a 180% increase in peak intracellular Ca 2+ ; addition of histamine increased intracellular Ca 2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca 2+ flux in human RPE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66430/1/j.1471-4159.1991.tb03471.x.pd

Evaluation of the Emergency Response Dose Assessment System(ERDAS)

The emergency response dose assessment system (ERDAS) is a protype software and hardware system configured to produce routine mesoscale meteorological forecasts and enhanced dispersion estimates on an operational basis for the Kennedy Space Center (KSC)/Cape Canaveral Air Station (CCAS) region. ERDAS provides emergency response guidance to operations at KSC/CCAS in the case of an accidental hazardous material release or an aborted vehicle launch. This report describes the evaluation of ERDAS including: evaluation of sea breeze predictions, comparison of launch plume location and concentration predictions, case study of a toxic release, evaluation of model sensitivity to varying input parameters, evaluation of the user interface, assessment of ERDA's operational capabilities, and a comparison of ERDAS models to the ocean breeze dry gultch diffusion model

Cruciferous vegetable supplementation in a controlled diet study alters the serum peptidome in a GSTM1-genotype dependent manner

<p>Abstract</p> <p>Background</p> <p>Cruciferous vegetable intake is inversely associated with the risk of several cancers. Isothiocyanates (ITC) are hypothesized to be the major bioactive constituents contributing to these cancer-preventive effects. The polymorphic glutathione-<it>S</it>-transferase (GST) gene family encodes several enzymes which catalyze ITC degradation <it>in vivo</it>.</p> <p>Methods</p> <p>We utilized high throughput proteomics methods to examine how human serum peptides (the "peptidome") change in response to cruciferous vegetable feeding in individuals of different <it>GSTM1 </it>genotypes. In two randomized, crossover, controlled feeding studies (EAT and 2EAT) participants consumed a fruit- and vegetable-free basal diet and the basal diet supplemented with cruciferous vegetables. Serum samples collected at the end of the feeding period were fractionated and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry spectra were obtained. Peak identification/alignment computer algorithms and mixed effects models were used to analyze the data.</p> <p>Results</p> <p>After analysis of spectra from EAT participants, 24 distinct peaks showed statistically significant differences associated with cruciferous vegetable intake. Twenty of these peaks were driven by their <it>GSTM1 </it>genotype (i.e., <it>GSTM1+ </it>or <it>GSTM1- </it>null). When data from EAT and 2EAT participants were compared by joint processing of spectra to align a common set, 6 peaks showed consistent changes in both studies in a genotype-dependent manner. The peaks at 6700 <it>m/z </it>and 9565 <it>m/z </it>were identified as an isoform of transthyretin (TTR) and a fragment of zinc α2-glycoprotein (ZAG), respectively.</p> <p>Conclusions</p> <p>Cruciferous vegetable intake in <it>GSTM1+ </it>individuals led to changes in circulating levels of several peptides/proteins, including TTR and a fragment of ZAG. TTR is a known marker of nutritional status and ZAG is an adipokine that plays a role in lipid mobilization. The results of this study present evidence that the <it>GSTM1</it>-genotype modulates the physiological response to cruciferous vegetable intake.</p

Interpretation time of serial chest CT examinations with stacked-metaphor workstation versus film alternator

PURPOSE: Interpretation time of serial staging chest CT cases, which each contained current and previous examinations, with a simple prototype workstation called filmstack was experimentally compared with interpretation time with a film alternator. MATERIALS AND METHODS: The filmstack displayed a "stack" of sections for each examination; user controls allowed rapid selection of preset attenuation windows and both synchronized and unsynchronized scrolling. Eight radiologists were timed as they used the filmstack and the film alternator to interpret four ergonomically complex serial CT cases. RESULTS: All reports dictated on the basis of findings with filmstack and film were of acceptable clinical accuracy. The time to examine a case with filmstack was significantly faster than the time with film, including the time to load and unload the alternator (99% confidence [P = .01]). There was no statistically significant difference in interpretation time between filmstack and prehung film. CONCLUSION: Use of a low-cost stacked CT workstation with a single 1,024 x 1,024 monitor is an effective means of interpreting cases that require comparison of multiple CT examinations

Asthma-susceptibility variants identified using probands in case-control and family-based analyses

<p>Abstract</p> <p>Background</p> <p>Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.</p> <p>Methods</p> <p>We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings.</p> <p>Results</p> <p>We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung.</p> <p>Conclusions</p> <p>Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.</p

SOCS2 Influences LPS Induced Human Monocyte-Derived Dendritic Cell Maturation

Dendritic cells (DCs) are highly specific antigen presenting cells, which link innate and adaptive immune responses and participate in protecting hosts from invading pathogens. DCs can be generated in vitro by culturing human monocytes with GM-CSF and IL-4 followed by LPS induced DC maturation. We set out to study the suppressor of cytokine signaling (SOCS) proteins during maturation and activation of human monocyte-derived DCs from peripheral blood in vitro. We found that the expression of SOCS2 mRNA and protein is dramatically up-regulated during DC maturation. Silencing of SOCS2 using siRNA, inhibited DC maturation as evidenced by a decreased expression of maturation markers such as CD83, co-stimulatory molecules CD40, CD86 and HLA-DR. Furthermore, silencing of SOCS2 decreased LPS induced activation of MAP kinases (SAKP/JNK, p38, ERK), IRF3, decreased the translocation of the NF-κB transcription factor and reduced downstream gene mRNA expression. These results suggest a role for SOCS2 in the MyD88-dependent and -independent TLR4 signaling pathways. In conclusion, our results demonstrate that SOCS2 is required for appropriate TLR4 signaling in maturating human DCs via both the MyD88-dependent and -independent signaling pathway

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NSO7040)National Institutes of Health (Grant 5 R01 NS04332)National Institutes of Health (Grant 5 R01 NS21183)National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 1 PO1-NS23734)National Science Foundation (Grant BNS 8418733)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0290)National Institutes of Health (Grant RO1-NS21183), subcontract with Boston UniversityNational Institutes of Health (Grant 1 PO1-NS23734), subcontract with the Massachusetts Eye and Ear Infirmar

Speech Communication

Contains table of contents for Part IV, table of contents for Section 1 and reports on five research projects.Apple Computer, Inc.C.J. Lebel FellowshipNational Institutes of Health (Grant T32-NS07040)National Institutes of Health (Grant R01-NS04332)National Institutes of Health (Grant R01-NS21183)National Institutes of Health (Grant P01-NS23734)U.S. Navy / Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Office of Naval Research (Contract N00014-82-K-0727